Integrated virtual screening and MD simulation study to discover potential inhibitors of Lyn-kinase: targeting cancer therapy.

Tyrosine-protein kinase Lyn (LynK) has emerged as one of the most attractive therapeutic targets for cancer and diabetes. In this study, we used a multistep virtual screening process of natural compounds to discover potential inhibitors of LynK from the IMPPAT database. The primary filters were based on Lipinski rules, ADMET properties, and PAINS patterns.

Abnormalities in sex hormones and sexual dysfunction in males with diabetes mellitus: A mechanistic insight.

Diabetes is a considerate metabolic disorder that can lead to a series of complications, involving the malfunctioning of the reproductive system of males. It has been observed that there is a gradual rise in male diabetic patients and almost half of the diabetic males have low semen quality and decrease reproductive function. In diabetic conditions, prolonged hyperglycemia leads to oxidative stress, diabetic neuropathy, and insulin resistance.

Synthesis and Anticancer Evaluation of Novel Indole Based Arylsulfonylhydrazides against Human Breast Cancer Cells.

A series of novel indole based sulfonohydrazide derivatives (-) containing morpholine heterocyclic ring were synthesized through multistep chemical reactions. The target compounds (-) were prepared by the reaction of substituted phenyl sulfonylhydrazides (-) with morpholine derivative of indole 3-carboxaldehyde. All the target compounds were screened for their anticancer activity against the estrogen receptor-positive breast cancer line MCF-7 and triple-negative breast cancer cell line, MDA-MB-468.

Measuring Structural Changes in Cytochrome under Crowded Conditions Using In Vitro and In Silico Approaches.

It is known from in vitro studies that macromolecular crowding in the cell effects protein structure, stability and function; but predictive studies are relatively unexplored. There are few reports where the effect of various crowder mixtures has been exploited to discern their combined effect on the structural stability of proteins. These studies are more significant because their effect can mimicked with in vivo conditions, where the environment is heterogeneous.

Intrinsically disordered regions in the rodent hepevirus proteome.

Hepatitis E virus (HEV) is the causative agent of Hepatitis E infections across the world. Intrinsically disordered protein regions (IDPRs) or intrinsically disordered proteins (IDPs) are regions or proteins that are characterized by lack of definite structure. These IDPRs or IDPs play significant roles in a wide range of biological processes, such as cell cycle regulation, control of signaling pathways, etc.

Structure-Guided Approach to Discover Tuberosin as a Potent Activator of Pyruvate Kinase M2, Targeting Cancer Therapy.

Metabolic reprogramming is a key attribute of cancer progression. An altered expression of pyruvate kinase M2 (PKM2), a phosphotyrosine-binding protein is observed in many human cancers. PKM2 plays a vital role in metabolic reprogramming, transcription and cell cycle progression and thus is deliberated as an attractive target in anticancer drug development.

Mechanistic Insight into the Binding of Huperzine a with Human Transferrin: Computational, Spectroscopic and Calorimetric Approaches.

Huperzine A (HupA), an alkaloid found in the club moss , has been in use for centuries in Chinese traditional medicine to treat dementia owing to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), thus acting as an acetylcholinesterase inhibitor (AChEI). An imbalance of metal ions in the brain is linked to Alzheimer's disease (AD) pathology. Transferrin (Tf) is a crucial player in iron homeostasis, thus highlighting its significance in AD.

Unravelling hub genes as potential therapeutic targets in lung cancer using integrated transcriptomic meta-analysis and in silico approach.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Smoking has been identified as the main contributing cause of the disease's development. The study aimed to identify the key genes in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the two major types of LC.

Targeting inhibition of microtubule affinity regulating kinase 4 by Harmaline: Strategy to combat Alzheimer's disease.

Microtubule-affinity regulating kinase 4 (MARK4) is linked with the development of cancer, diabetes and neurodegenerative diseases. Due to its direct role in the hyperphosphorylation of tau protein, MARK4 is considered as an attractive target to fight Alzheimer's disease (AD) and neuroinflammation. In the present study, we have selected Harmaline (HAR), an alkaloid of Paganum harmala, to investigate its MARK4 inhibitory potential and its binding mechanism.

Unravelling Binding of Human Serum Albumin with Galantamine: Spectroscopic, Calorimetric, and Computational Approaches.

Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer's disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements.

Circulation of DENV-3 Genotype 3 during 2017 to 2018 in Delhi: A Single-Center Hospital-Based Study.

 Delhi is hyperendemic for dengue virus (DENV) where all the four DENV have previously been reported. A constant vigilance of circulating DENV serotypes is important in surveillance, since the introduction of a new variant to areas affected by preexisting serotypes constitutes a risk factor for dengue hemorrhagic fever and dengue shock syndrome.  This retrospective study was performed with an objective to determine the circulating serotype and genotype of DENV in acute phase blood samples of patients who have reported to a tertiary liver care hospital in New Delhi during the last 2 years (2017-2018).

Pan-cancer analysis of Chromobox (CBX) genes for prognostic significance and cancer classification.

Polycomb group of proteins play a significant role in chromatin remodelling essential for epigenetic regulation of transcription. Chromobox (CBX) gene family is an important part of canonical polycomb repressive complex 1 (PRC1), belonging to the polycomb group involved in chromatin remodelling. Aberrations in CBX expression are linked to various cancers.

Unravelling the role of telomere shortening with ageing and their potential association with diabetes, cancer, and related lifestyle factors.

Telomeres are often considered as the 'ageing clock' that determines the lifespan at the cellular level, forming the ends of a chromosome, which shorten each time the cell divides itself to the point where they become so short the cell is unable to divide itself further. Telomere length alteration is often linked with lifestyle factors such as age, obesity, exposure to pesticides and pollution, depression, unhealthy diet, lack of exercise, and stress. The current review discusses the mechanism of telomere shortening in relation to ageing and lifestyle factors in general and its association with chronic diseases like diabetes which may influence the health and lifespan of an individual by increasing telomere shortening.

Spectroscopic and DFT study of imidazolium based ionic liquids with broad spectrum antibacterial drug levofloxacin.

Herein, we have shown the interaction of levofloxacin (LVF) with two imidazolium based ionic liquids (ILs), 1-butly-3-methylimidazolium chloride ([Bmim][Cl]) and 1-decyl-3-methylimidazolium chloride ([Dmim][Cl]) by utilising spectroscopic techniques along with computational approach. Both [Bmim][Cl] and [Dmim][Cl] quenched the fluorescence emission of LVF suggesting complex formation between ILs and the drug. The steady-state and time-resolve fluorescence studies revealed that the quenching of fluorescence emission of LVF in the presence of [Bmim][Cl] and [Dmim][Cl], which signified the non-fluorescent complex formation between LVF and ILs.

Pharmacological features, health benefits and clinical implications of honokiol.

Honokiol (HNK) is a natural polyphenolic compound extracted from the bark and leaves of It has been traditionally used as a medicinal compound to treat inflammatory diseases. HNK possesses numerous health benefits with a minimal level of toxicity. It can cross the blood-brain barrier and blood-cerebrospinal fluid, thus having significant bioavailability in the neurological tissues.

Investigating neuroprotective roles of Bacopa monnieri extracts: Mechanistic insights and therapeutic implications.

Bacopa monnieri (Brahmi) is a well-known perennial, creeping herb of the Indian Ayurveda system; it contains numerous bioactive phytoconstituents implicated in the therapeutic management of several life-threatening diseases. This herb was used by Ancient Vedic scholars due to its pharmacological effect, especially as a nerve tonic and nootropic booster. However, to better understand the roles of Bacopa monnieri extract (BME) in neurological disorders and memory-related diseases, it is necessary to understand its active phytochemical constituents and their molecular mechanisms.

Pharmacological attributes of extract: Current updates and clinical manifestation.

has been used for centuries in Ayurvedic medicine, alone or in combination with other herbs, as a memory and learning enhancer, sedative, and anti-epileptic. This review aimed to highlight the health benefits of extracts (BME), focusing on anti-cancer and neurodegenerative diseases. We examined the clinical studies on phytochemistry and pharmacological application of BME.

Identification of two novel thiazolidin-2-imines as tyrosinase inhibitors: synthesis, crystal structure, molecular docking and DFT studies.

Various - and -containing 5-membered heterocycles such as imidazole-2-thiones, thiazolidinones and thiazolidin-2-imines are among the most eminent biologically active organic heterocycles and are present in many marketed drugs. In view of their synthetic and biological significance, an efficient synthesis of two novel thiazolidine-2-imines () utilizing a three-component one-pot approach starting from an aldimine, an alkyne and isothiocyanates has been developed. The reaction proceeded a ( cyclization of a propargyl thiourea, formed in the presence of Zn-catalyst.

Identification of pathogenic genes associated with CKD: An integrated bioinformatics approach.

Chronic kidney disease (CKD) is defined as a persistent abnormality in the structure and function of kidneys and leads to high morbidity and mortality in individuals across the world. Globally, approximately 8%-16% of the population is affected by CKD. Proper screening, staging, diagnosis, and the appropriate management of CKD by primary care clinicians are essential in preventing the adverse outcomes associated with CKD worldwide.

-Guggulsterone Is a Potential Lead Molecule of Dawa-ul-Kurkum against Hepatocellular Carcinoma.

An ancient saffron-based polyherbal formulation, Dawa-ul-Kurkum (DuK), has been used to treat liver ailments and other diseases and was recently evaluated for its anticancer potential against hepatocellular carcinoma (HCC) by our research team. To gain further insight into the lead molecule of DuK, we selected ten active constituents belonging to its seven herbal constituents (crocin, crocetin, safranal, jatamansone, isovaleric acid, cinnamaldehyde, coumaric acid, citral, guggulsterone and dehydrocostus lactone). We docked them with 32 prominent proteins that play important roles in the development, progression and suppression of HCC and those involved in endoplasmic reticulum (ER) stress to identify the binding interactions between them.

Fabrication and Characterization of Acute Myocardial Infarction Myoglobin Biomarker Based on Chromium-Doped Zinc Oxide Nanoparticles.

In this article, we describe the fabrication and characterization of a sensor for acute myocardial infarction that detects myoglobin biomarkers using chromium (Cr)-doped zinc oxide (ZnO) nanoparticles (NPs). Pure and Cr-doped ZnO NPs (13 × 10, 20 × 10, and 32 × 10 atoms/cm in the solid phase) were synthesized by a facile low-temperature sol-gel method. Synthesized NPs were examined for structure and morphological analysis using various techniques to confirm the successful formation of ZnO NPs.

Mathematical modeling in perspective of vector-borne viral infections: a review.

Background: Viral diseases are highly widespread infections caused by viruses. These viruses are passing from one human to other humans through a certain medium. The medium might be mosquito, animal, reservoir and food, etc.

Identifying Isoononin and Candidissiol as Rho-associated protein kinase 1 (ROCK1) inhibitors: a combined virtual screening and MD simulation approach.

Rho-associated protein kinase 1 (ROCK1) is a member of the AGC family which plays crucial roles in inflammatory diseases and cancer progression. Elevated expression of ROCK1 has been reported in multiple cancer types, and thus it has emerged as a potential drug target for cancer therapeutics. In this study, we performed a structure-based virtual screening of the natural compounds taken from the IMPPAT database to find some potential molecules as inhibitors of ROCK1.

Microtubule-affinity regulating kinase 4: A potential drug target for cancer therapy.

The human genome encodes more than 500 protein kinases that work by transferring the γ-phosphate group from ATP to serine, threonine, or tyrosine (Ser/Thr/Tyr) residues. Various kinases are associated with the onset of cancer and its further progression. The recent advancements in developing small-molecule kinase inhibitors to treat different cancer types have shown noticeable results in clinical therapies.